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Treacher Collins syndrome 3(TCS3)

MedGen UID:
340868
Concept ID:
C1855433
Disease or Syndrome
Synonyms: Mandibulofacial dysostosis, Treacher Collins type, autosomal recessive; POLR1C-Related Treacher Collins Syndrome; TCS3
 
Gene (location): POLR1C (6p21.1)
 
Monarch Initiative: MONDO:0009558
OMIM®: 248390

Disease characteristics

Excerpted from the GeneReview: Treacher Collins Syndrome
Treacher Collins syndrome (TCS) is characterized by lower eyelid abnormalities, malar hypoplasia, downslanted palpebral fissures, and micro- or retrognathia due to symmetric hypoplasia of the zygomatic bones, maxilla, and mandible. External ear anomalies include absent, small, malformed, and/or posteriorly rotated ears and atresia or stenosis of the external auditory canals. About 40%-50% of individuals have conductive hearing loss attributed most commonly to malformation of the ossicles and hypoplasia of the middle ear cavities. Inner ear structures tend to be normal. Significant respiratory and feeding difficulties can be present in infancy. Other, less common abnormalities include cleft palate and unilateral or bilateral choanal stenosis or atresia. Typically, intellect is normal. [from GeneReviews]
Authors:
Mafalda Barbosa  |  Ethylin Wang Jabs  |  Sara Huston   view full author information

Additional description

From OMIM
Treacher Collins syndrome is a disorder of craniofacial development characterized by a combination of bilateral downward slanting of the palpebral fissures, colobomas of the lower eyelids with a paucity of eyelashes medial to the defect, hypoplasia of the facial bones, cleft palate, malformation of the external ears, atresia of the external auditory canals, and bilateral conductive hearing loss (Dauwerse et al., 2011). For additional phenotypic information and a discussion of genetic heterogeneity of Treacher Collins syndrome, see TCS1 (154500).  http://www.omim.org/entry/248390

Clinical features

From HPO
Conductive hearing impairment
MedGen UID:
9163
Concept ID:
C0018777
Disease or Syndrome
An abnormality of vibrational conductance of sound to the inner ear leading to impairment of sensory perception of sound.
Microtia
MedGen UID:
57535
Concept ID:
C0152423
Congenital Abnormality
Underdevelopment of the external ear.
Micrognathia
MedGen UID:
44428
Concept ID:
C0025990
Congenital Abnormality
Developmental hypoplasia of the mandible.
Malar flattening
MedGen UID:
347616
Concept ID:
C1858085
Finding
Underdevelopment of the malar prominence of the jugal bone (zygomatic bone in mammals), appreciated in profile, frontal view, and/or by palpation.
Hypoplasia of the zygomatic bone
MedGen UID:
866886
Concept ID:
C4021242
Anatomical Abnormality
Underdevelopment of the zygomatic bone. That is, a reduction in size of the zygomatic bone, including the zygomatic process of the temporal bone of the skull, which forms part of the zygomatic arch.
Mandibulofacial dysostosis
MedGen UID:
505796
Concept ID:
CN004722
Disease or Syndrome
Treacher Collins syndrome (TCS) is a disorder of craniofacial development. The features include downslanting palpebral fissures, coloboma of the eyelid, micrognathia, microtia and other deformity of the ears, hypoplastic zygomatic arches, and macrostomia. Conductive hearing loss and cleft palate are often present (summary by Dixon, 1996). Genetic Heterogeneity of Treacher Collins Syndrome Treacher Collins syndrome-2 (TCS2; 613717) is caused by mutation in the POLR1D gene (613715) on chromosome 13q12. Treacher Collins syndrome-3 (TCS3; 248390) is caused by mutation in the POLR1C gene (610060) on chromosome 6p21. Treacher Collins syndrome-4 (TCS4; 618939) is caused by mutation in the POLR1B gene (602000) on chromosome 2q14.
Downslanted palpebral fissures
MedGen UID:
98391
Concept ID:
C0423110
Finding
The palpebral fissure inclination is more than two standard deviations below the mean.
Lower eyelid coloboma
MedGen UID:
373417
Concept ID:
C1837826
Disease or Syndrome
A short discontinuity of the margin of the lower eyelid.
Cleft palate
MedGen UID:
756015
Concept ID:
C2981150
Congenital Abnormality
Cleft palate is a developmental defect of the palate resulting from a failure of fusion of the palatine processes and manifesting as a separation of the roof of the mouth (soft and hard palate).

Professional guidelines

PubMed

Johns AL, Stock NM, Costa B, Billaud Feragen K, Crerand CE
Cleft Palate Craniofac J 2023 Sep;60(9):1090-1112. Epub 2022 Apr 5 doi: 10.1177/10556656221091699. PMID: 35382590Free PMC Article
Chan CH, Hu AC, Jain NS, Dang BN, Liu MT, Bertrand AA, Wilson LF, Lee JC
J Craniofac Surg 2021 Nov-Dec 01;32(8):2771-2773. doi: 10.1097/SCS.0000000000007938. PMID: 34727477
Xu X, Wang B, Jiang Z, Chen Q, Mao K, Shi X, Yan C, Hu J, Zha Y, Ma C, Zhang J, Guo R, Wang L, Zhao S, Liu H, Zhang Q, Zhang YB
Hum Mol Genet 2021 May 31;30(11):1045-1056. doi: 10.1093/hmg/ddab055. PMID: 33615373

Recent clinical studies

Diagnosis

Stoll C, Alembick Y, Roth MP
Am J Med Genet A 2023 Sep;191(9):2312-2323. Epub 2023 Jul 21 doi: 10.1002/ajmg.a.63344. PMID: 37477275

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